1. Field of the Invention
This invention relates to the use of a protic solvent in nucleophilic displacement reactions.
2. Description of the Related Art
Nucleophilic substitution of alkyl halides is perhaps one of the most useful reactions in organic chemistry. The nucleophilic displacement of chloride ion and similar leaving groups (e.g. bromide ion, sulfonate ion) is usually performed under anhydrous conditions using polar aprotic solvents or alcoholic solvents, or heterogeneous phase transfer conditions. This is especially true for very reactive substrates, since protic solvents (or water) might lead to solvolysis of these substrates.
One such example of very reactive intermediates is the sulfonium ion that forms in nucleophilic displacement reactions of β-chlorosulfides. As fast as it is formed, this intermediate reacts with water to yield the corresponding solvolysis product. Thus, known procedures for the nucleophilic displacement of such compounds typically employ aprotic solvents (THF, DMF, DMSO, MeCN), or alcoholic solvents (EtOH), phase transfer conditions or no solvent (Ohsawa et al., J. Org. Chem. 1983 48, 3644; Tolstikov et al., Khim-Farm. Zh. 1997 31 (8), 26-29; Krivonogov et al., Khim-Farm. Zh. 1995 29 (4), 38-40). Usually these procedures require harsh conditions (e.g. temperatures over 100° C.) and, as such, products are isolated in poor to moderate yields. A procedure that reduces reaction time and increases reaction yield is desired.